Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents

doi:10.1021/acschemneuro.8b00357

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents
	Xu, Yixiang 3; Zhang, Jian 1; Wang, Huan 1; Mao, Fei 2; Bao, Keting 2; Liu, Wenwen 2; Zhu, Jin 2; Li, Xiaokang 2; Zhang, Haiyan1 ; Li, Jian 3
刊名	ACS chemical neuroscience
	2018-08-29
ISSN号	1948-7193
DOI	10.1021/acschemneuro.8b00357
文献子类	Article
英文摘要	Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases (MAOs) are promising therapy for Alzheimer's disease (AD). Herein, a series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed and synthesized as dual inhibitors of ChEs and MAOs with other functions against AD. Most of these derivatives inhibited ChEs and MAOs with IC values in the micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of targeting the AChE (IC = 0.032 ± 0.007 μM) and MAO-B (IC = 2.117 ± 0.061 μM), along with the improved blood-brain barrier (BBB) permeability, antioxidant ability, and good copper chelating property in vitro. Animal studies showed that compound 1c·HCl could inhibit the cerebral AChE/MAO-B activities and alleviate scopolamine-induced cognitive impairment in mice. Combined with good oral bioavailability ( F = 45.55%), these findings demonstrated that compound 1c may be a potent brain permeable multifunctional candidate for the treatment of AD.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266279]
专题	药理学第二研究室
作者单位	1.CAS Key Laboratory of Receptor Research , Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road , Shanghai 201203 , China; 2.Shanghai Key Laboratory of New Drug Design, School of Pharmacy , East China University of Science and Technology , 130 Mei Long Road , Shanghai 200237 , China 3.State Key Laboratory of Bioreactor Engineering , East China University of Science and Technology , 130 Mei Long Road , Shanghai 200237 , China;
推荐引用方式 GB/T 7714	Xu, Yixiang,Zhang, Jian,Wang, Huan,et al. Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents[J]. ACS chemical neuroscience,2018.
APA	Xu, Yixiang.,Zhang, Jian.,Wang, Huan.,Mao, Fei.,Bao, Keting.,...&Li, Jian.(2018).Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents.ACS chemical neuroscience.
MLA	Xu, Yixiang,et al."Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents".ACS chemical neuroscience (2018).